Diabetes mellitus, also commonly referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the pancreas does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).
All forms of diabetes are associated with increased risk of long-term serious health complications. These may typically develop after several years of diabetes. The major long-term complications relate to various manifestations of damage to blood vessels. Such manifestations include eye diseases, cardiovascular diseases, ischemic heart disease, including angina and myocardial infarction, stroke and peripheral vascular disease. A related risk is diabetic neuropathy, the impact of diabetes on the nervous system, which can cause numbness, tingling and pain in the feet, and eventually lead to diabetes-related foot problems, such as diabetic foot ulcers, that can be difficult to treat and in some cases can require amputation.
There are two major types of diabetes. Type 1 diabetes is partly inherited and unrelated to lifestyle, and generally at its outset can be triggered by certain infections. Patients will often acquire type 1 diabetes at a young age. Type 2 diabetes is primarily caused by certain lifestyle factors, including obesity, lack of physical activity, and poor diet, and is often associated with old age.
Globally, as of 2010, it was estimated that almost 300 million people had diabetes, with type II accounting for approximately 90% of the cases. Diabetes is recognized as an evolving global epidemic with an expectation that the number of cases will double from 2010 to 2030. Diabetes is common throughout the world, but is more prevalent in developed countries. It is expected that the growth rate of diabetes type II will be largest in Asia and Africa, as developing nations on these continents become more urbanized, and adopt a “westernized” lifestyle and diet, so that nations in these countries will eventually form the majority of new cases of diabetes mellitus.
In conjunction with the rapid worldwide growth of diabetes, it is an increasing global health management risk that many cases of diabetes remain undiagnosed until a late stage, and particularly in developing countries, high cost of medication may further prevent the initiation of proper treatment.
In recent years, scientific evidence has accumulated, showing that bariatric surgery can reverse type 2 diabetes, with evidence from studies over the past more than 10 years that resolution of type 2 diabetes is often observed as an additional outcome of surgical treatment of morbid obesity.
Many of these studies have also shown that diabetes-related morbidity and mortality declines significantly postoperatively, and that this improvement in diabetes control is long lasting. Bypass procedures, particularly the Roux-en-Y gastric bypass (RYGBP) and the biliopancreatic diversion (BPD), have proven more effective treatments for diabetes, as compared to other procedures and are associated with normalization of plasma glucose, insulin, and Glycated hemoglobin levels in more than 80% of morbidly obese patients undergoing these procedures (Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 2009;122:248-256, e5).
Studies indicate that these effects are nearly immediate, taking effect within hours or days after surgery, and are therefore not principally caused by longer-term weight-loss. The exact causes are unknown, but current hypothesis are for example: decreased absorption or partial malabsorption of nutrients, or anatomical alteration of the gastrointestinal tract causing a changed dynamic behavior of the incretin system.
Recently several studies report that invasive or noninvasive implantation of a sleeve in the small intestine, covering an initial intestine segment just beyond the stomach, can quickly improve glycemic control in obese diabetes patients.
For example, a small study of patients that received a duodenal-jejunal bypass liner implant (EndoBarrier™), reported that fasting plasma glucose levels fell 55 mg/dL, while levels among those who had a non-effective control procedure rose. The positive results proved to not be lasting over a period of a year, in part due to complications causing need for removal before trial expiration. (Rodriquez L, et al “Pilot clinical study of an endoscopic, removable duodenal-jejunal bypass liner for the treatment of type 2 diabetes” Diabetes Tech & Therapeutics 2009; DOI: 10.1089/dia.2009.0063.).
However, despite positive impact on diabetes from bypass bariatric surgery and intestinal sleeve procedures, significant morbidity and mortality risks are directly associated with such invasive surgical or device implantation procedures.
As such, considering the foregoing, it may be appreciated that there continues to be a need for novel and improved pharmaceutical compositions and methods for treating diabetes.